Photometric surveys such as Kepler have the precision to identify exoplanet and eclipsing binary candidates from only a single transit. K2, with its 75 d campaign duration, is ideally suited to ...detect significant numbers of single-eclipsing objects. Here we develop a Bayesian transit-fitting tool (‘Namaste: An Mcmc Analysis of Single Transit Exoplanets’) to extract orbital information from single transit events. We achieve favourable results testing this technique on known Kepler planets, and apply the technique to seven candidates identified from a targeted search of K2 campaigns 1, 2 and 3. We find EPIC203311200 to host an excellent exoplanet candidate with a period, assuming zero eccentricity, of
$540 ^{+410}_{-230}$
d and a radius of 0.51 ± 0.05R
Jup. We also find six further transit candidates for which more follow-up is required to determine a planetary origin. Such a technique could be used in the future with TESS, PLATO and ground-based photometric surveys such as NGTS, potentially allowing the detection of planets in reach of confirmation by Gaia.
We report the discovery of the exoplanet K2-110 b (previously EPIC212521166b) from K2 photometry orbiting in a 13.8637d period around an old, metal-poor K3 dwarf star. With a V-band magnitude of ...11.9, K2-110 is particularly amenable to RV follow-up. A joint analysis of K2 photometry and high-precision RVs from 28 HARPS and HARPS-N spectra reveal it to have a radius of 2.6 ± 0.1R⊕ and a mass of 16.7 ± 3.2M⊕, hence a density of 5.2 ± 1.2 g cm-3, making it one of the most massive planets yet to be found with a sub-Neptune radius. When accounting for compression, the resulting Earth-like density is best fitted by a 0.2M⊕ hydrogen atmosphere over an 16.5M⊕ Earth-like interior, although the planet could also have significant water content. At 0.1 AU, even taking into account the old stellar age of 8 ± 3 Gyr, the planet is unlikely to have been significantly affected by EUV evaporation. However the planet likelydisc-migrated to its current position making the lack of a thick H2 atmosphere puzzling. This analysis has made K2-110 b one of the best-characterised mini-Neptunes with density constrained to less than 30%.
We have used the WASP survey to discover two exoplanetary systems, each consisting of a Jupiter-sized planet transiting an 11th-magnitude (V) main-sequence star. WASP-104b orbits its star in 1.75 d, ...whereas WASP-106b has the fourth-longest orbital period of any planet discovered by means of transits observed from the ground, orbiting every 9.29 d. Each planet is more massive than Jupiter (WASP-104b has a mass of 1.27 ± 0.05MJup, while WASP-106b has a mass of 1.93 ± 0.08MJup). Both planets are just slightly larger than Jupiter, with radii of 1.14 ± 0.04 and 1.09 ± 0.04RJup for WASP-104 and WASP-106, respectively. No significant orbital eccentricity is detected in either system, and while this is not surprising in the case of the short-period WASP-104b, it is interesting in the case of WASP-106b, because many otherwise similar planets are known to have eccentric orbits.
•Retinal effects were observed in nonclinical studies with a drug candidate.•Light induced retinal degeneration occurred in non-pigmented but not pigmented rats.•Reversible ERG effects with no ...histological correlates were observed in monkeys.•Results suggest that the effects are neuromodulatory and not neurotoxic.•Results supported safe testing in a clinical proof of concept study with monitoring.
The development path described for JNJ-26489112 provides perspectives on interpretation of retinal effects observed in nonclinical studies and their implications for clinical development. JNJ-26489112 is a CNS-active investigational drug that has potential as a novel treatment for treatment-resistant and bipolar depression, epilepsy, and neuropathic/inflammatory pain. In a 6-month toxicity study in albino rats, retinal atrophy was observed at supratherapeutic exposures to JNJ-26489112. The histopathological changes and topography of the lesions were characteristic of light-induced damage specific to albino rats. The species/strain specificity is supported by an absence of any ocular effects in dogs and in pigmented and albino rats, housed under standard and reduced lighting, respectively. To further evaluate its potential to cause ocular effects, in vivo functional and structural ocular analyses were included in a 9-month monkey toxicity study. Reductions in rod- and cone-mediated electroretinograms were observed at supratherapeutic exposures but without any histopathologic changes. These data suggested that the effects of JNJ-26489112 in monkeys were neuromodulatory and not neurotoxic. Taken together, data related to the light-induced atrophy in albino rats and reversible neuromodulatory effects in monkeys, supported the safe evaluation of JNJ-26489112 in a clinical proof-of-concept study that included comprehensive functional and structural ocular monitoring.
Abstract Though gold nanoparticles have been considered bio-inert, recent studies have questioned their safety. To reduce the potential for toxicity, we developed a nanoclustering of gold and iron ...oxide as a nanoparticle (nanorose) which biodegrades into subunits to facilitate rapid excretion. In this present study, we demonstrate acid and macrophage lysosomal degradation of nanorose via loss of the near-infrared optical shift, and clearance of the nanorose in vivo following i.v. administration in C57BL/6 mice by showing gold concentration is significantly reduced in 11 murine tissues in as little as 31 days ( P < 0.01). Hematology and chemistry show no toxicity of nanorose injected mice up to 14 days after administration. We conclude that the clustering design of nanorose does enhance the excretion of these nanoparticles, and that this could be a viable strategy to limit the potential toxicity of gold nanoparticles for clinical applications. From the Clinical Editor The potential toxicity of nanomaterials is a critically important limiting factor in their more widespread clinical application. Gold nanoparticles have been classically considered bio-inert, but recent studies have questioned their safety. The authors of this study have developed a clustering gold and iron oxide nanoparticle (nanorose), which biodegrades into subunits to facilitate rapid excretion, resulting in reduced toxicity.
Background Community-acquired respiratory distress syndrome (CARDS) toxin is a unique Mycoplasma pneumoniae virulence factor. Molecular assays targeting this toxin are more sensitive than existing ...diagnostics, but these assays have not been used to investigate the role of M pneumoniae as a nosocomial infection in critical illness. We sought to determine the incidence of M pneumoniae among mechanically ventilated subjects using these novel assays and to investigate the impact of this pathogen on pulmonary outcomes. Methods We conducted a prospective observational study enrolling subjects with suspected ventilator-associated pneumonia (VAP) undergoing BAL in the surgical trauma ICU at a level I trauma center. Lavage fluid and serum samples were tested for M pneumoniae using assays to detect CARDS toxin gene sequences, protein, or antitoxin antibodies. Results We collected samples from 37 subjects, with 41% (15 of 37) testing positive using these assays. The positive and negative groups did not differ significantly in baseline demographic characteristics, including age, sex, injury severity, or number of ventilator days before bronchoscopy. The positive group had significantly fewer ventilator-free days ( P = .04) and lower average oxygenation ( P = .02). These differences were most pronounced among subjects with ARDS. Conclusions Evidence is provided that M pneumoniae is present in a substantial number of subjects with suspected VAP. Subjects testing positive experience a significantly longer ventilator course and worse oxygenation compared with subjects testing negative.
Abstract Background We recently described a new method of diagnosing anastomotic leak using the detection of electrical changes induced by electrolyte extravasation from a surgically created gastric ...leak site in experimental rats. We sought to compare the sensitivity and specificity of anastomotic leak detection for this method to that of upper gastrointestinal (GI) barium fluoroscopy. Methods Experimental rats with a surgically created gastric leak site and controls were interrogated as to the presence of leak using either the electrolyte-gated leak detection method or upper GI barium fluoroscopy. The sensitivity and specificity of leak detection for the two methods were compared. Results The sensitivity and specificity of electrolyte-gated leak detection were both 100% (95% confidence interval 69–100%). Barium upper GI fluoroscopy misidentified one leak as a control and one control as a leak, for a sensitivity and specificity of 80% each (95% confidence interval 37–97%). No statistically significant difference was seen between electrolyte-gated leak detection and barium upper GI fluoroscopy in terms of the sensitivity and specificity of anastomotic leak detection. Conclusions Electrolyte-gated leak detection was similarly sensitive and specific for anastomotic leak detection as upper GI barium fluoroscopy, the current standard. The electrolyte-gated method has the advantages of an inert contrast agent (normal saline) and the possibility of performing leak interrogation at the bedside. Electrolyte-gated leak detection might represent a plausible alternative to upper GI barium fluoroscopy for routine postoperative anastomotic leak surveillance after esophagectomy or other foregut surgery.
Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics ...and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus‐on‐a‐chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ‐level contributions to inflammation‐induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet‐endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor‐1 (PAR‐1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.
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